tbuckley/cabot-search huggingface dataset:
HER3 expression status following systemic chemotherapy treatment in biliary tract cancers.
Authors: Mariko Nishioka, Chigusa Morizane, Mao Okada, Tomoyuki Satake, Nobuyoshi Hiraoka, Satoshi Nara, Tomoya Kakegawa, Maki Kobayashi, Kumiko Koyama, Minoru Esaki, Takuji Okusaka
Journal: Journal of Clinical Oncology (2023)

e16153 Background: Erb-b2 receptor tyrosine kinase 3 (HER3) is frequently overexpressed in a variety of cancers. Activation of HER3 signaling serves an important role in promoting cell proliferation and is associated with chemoresistance. Thus, there is interest in exploring HER3 status of tumors as a potential prognostic and/or therapeutic target. Prior studies have reported HER3 status in various cancers after treatment with chemotherapy (CT). However, HER3 expression profile in biliary tract cancer (BTC) remains unknown. Here, we evaluated HER3 status of patients with BTC post CT. Methods: The medical records of patients (pts) who had been initially diagnosed with BTC and treated at the National Cancer Center Hospital (Tokyo, Japan), between January 2010 and June 2020, were retrospectively analyzed. Pts whose post CT specimens were available were included in this study. Immunohistochemical staining for HER3 was performed using HER3/ErbB3 (D22C5) XP Rabbit mAb (Cell Signaling Technology) as a primary antibody. IHC scoring (0, 1+, 2+, 3+) of membranous staining intensity was performed according to HER2 IHC gastric scoring guideline. Results: A total of 19 pts with BTC, with a median age of 59 (range 44-79) years, had specimens available after post CT and were evaluated for HER3 expression status. HER3 status was 3+ in 10 pts, 2+ in 3 pts, 1+ in 4 pts, and 0 in 2 pts. The specimens were obtained from liver in 17 pts, bone in 1 pt, and omental lymph node in 1 pt. The histological type was adenocarcinoma in all pts, and HER3 status according to primary tumor type is shown in the table below. Fourteen pts were treated with gemcitabine (GEM) plus cisplatin (CDDP), 1 pt with GEM plus CDDP plus S-1, 1 pt with GEM plus S-1 as first-line CT for advanced BTC, and 3 pts with S-1 as an adjuvant treatment. Fifteen pts were biopsied after CT to participate in clinical trial. The remaining 4 obtained specimens after CT during primary surgery or surgery for metastases or for cholangitis. The median overall survival of pts with advanced BTC was 23.6 months in HER3 3+, 17.1 months in HER3 2+, 27.7 months in HER3 1+, and 24.6 months in HER3 0. Four pts had specimens available from pre and post CT, all of which were intrahepatic cholangiocarcinoma with the treatment of GEM plus CDDP. HER3 status was upregulated in 3 pts (1 pt 1+ to 2+, 2 pts 2+ to 3+) and downregulated in 1 pt (1+ to 0) at post CT. Conclusions: HER3 expression (1+, 2+, 3+) was observed in 89.5% of previously treated pts with BTC, and HER3 status was upregulated after CT in some pts. These results suggest that HER3 might be a potential therapeutic target in BTC post CT. [Table: see text]
Luminal and basal subtyping of circulating tumor cells and influence on outcomes in patients with metastatic castration-resistant prostate cancer.
Authors: Jasmine Jiemei Wang, Minhyung Kim, Pai-Chi Teng, Yu Jen Jan, Jie-Fu Chen, Yazhen Zhu, Sungyong You, Hsian-Rong Tseng, Edwin Melencio Posadas
Journal: Journal of Clinical Oncology (2023)

e17034 Background: Luminal and basal subtyping using PAM50 classifier and the prostate cancer classification system (PCS) have been shown to predict outcomes and treatment response in prostate cancer (PCa). However, these genomic classifiers rely on the acquisition of tumor samples, which are usually not available in patients with metastatic castration resistant PCa (mCRPC). Circulating tumor cells (CTC) are tumors cells shed into bloodstream and can serve as surrogates of tumor. In this study, we aimed to subtype circulating tumor cells with PAM50 and PCS classifiers and evaluate their prognostic performance in mCRPC patients. Methods: A CTC RNA assay was developed by combining NanoVelcro microfluidic system for enriching CTCs and Nanostring nCounter system for PAM50 and PCS profiling of CTCs. The PAM50 and PCS genes were refined through a bioinformatic pipeline to ensure the specific profiling of CTCs. The classification and prognostic performance of the refined CTC-PAM50 and CTC-PCS gene panels were validated in GenomeDx GRID database. For the clinical study, 50 blood samples from mCRPC patients before the initiation of androgen receptor signaling inhibitors (ARSI) (n = 34) or taxanes (n = 16) were analyzed with the CTC RNA assay. Kaplan-Meier analysis and log-rank test were used to evaluate the association between CTC-PAM50/PCS subtypes and survival. Results: The refined CTC-PAM50 (36 genes) and CTC-PCS (40 genes) classifiers retained their original classification and prognostic performance in the GenomeDx GRID cohort. In the clinical study, the CTC RNA assay classified the 50 mCRPC patients into luminal A (n = 14), luminal B (n = 22), and basal (n = 14) by CTC-PAM50 classifier; and PCS1 (n = 5), PCS2 (n = 24), and PCS3 (n = 21) by CTC-PCS classifier. Overall, patients assigned as PCS1 subtype had shorter overall survival than other subtypes (hazard ratio [HR] = 4.8). In addition, basal or PCS1 subtype showed worse biochemical progression free survival than other subtypes (ARSI group: Basal: HR = 2.5; PCS1: HR = 6.9. Taxanes group: Basal: HR = 5.0; PCS1: HR = 7.2). Conclusions: Luminal and basal subtyping of CTCs is prognostic and provides a noninvasive method for molecular profiling mCRPC patients.
Association between hyperthyroidism and thyroid cancer in the Congolese hospital setting.
Authors: John Bukasa-Kakamba, Ayrton Bangolo, Sonia Onyeka, Sowmya Sagireddy, Mary Bangura, Joshua Rathod, Eugenio L. Gomez, Mansi Naria, Conrad Erikson, Erwin J. Tabucanon, Blanka Bortely, Juilee V. Dongre, Reshma Radhakrishnan, Aditya K.G. Tirumala, Amer Jarri, Vignesh Nagesh, Angel Ann Chacko, Shraboni Dey, Tracy Ann Proverbs-Singh, Simcha Weissman
Journal: Journal of Clinical Oncology (2023)

e18092 Background: Thyroid cancer accounts for 1% of cancers worldwide. Hyperthyroidism was long considered a protective factor against thyroid cancer. This association was rare in the literature and raised a lot of controversy in the scientific world. There are currently no studies carried out in the Congolese hospital setting to establish the association between hyperthyroidism and thyroid cancer. We hypothesize that there is an association between thyroid cancer and hyperthyroidism in the Congolese hospital setting. Methods: This is a descriptive and retrospective study, which involved 106 cases of thyroid cancer who underwent partial or total thyroidectomy and pathological examination in four laboratories in the city of Kinshasa between 2005 and 2019. These laboratories receive samples from all the medical centers in Kinshasa. Statistical analyses of the data were performed using Statistical Package for the social sciences (SPSS) for Windows version 22 software. Data were expressed as mean +/- standard deviation for metric parameters, and as absolute or relative frequencies in percentages for categorical parameters. For all tests used the p-value &lt; 0.05 was considered as the threshold of statistical significance. This research protocol was approved by the National Health Ethics Committee of the DRC No. 197/CNES/BN/PMMF/2020. Results: Out of 106 cases of thyroid cancer, the association of hyperthyroidism and thyroid cancer was found in 5 cases (4.7%) (3.6% for women vs. 9% for men). The mean age of patients with this association was 51 ± 11 years. Papillary carcinoma (two cases), follicular carcinoma (two cases) and lymphoma (one case) were the types of cancer encountered. Etiologically, toxic multinodular goiter (four cases; 80%) and toxic adenoma (one case; 2%) were found. Conclusions: There is an association between hyperthyroidism and thyroid cancer in the Congolese hospital setting. There is a predominance of the female gender. There was an equal number of papillary and follicular carcinomas. With this study, we hope to encourage clinicians to thoroughly evaluate any suspicious nodule associated with hyperthyroidism. [Table: see text]
Five-year subgroup analysis of tafasitamab + lenalidomide from the phase II L-MIND study in patients with relapsed or refractory diffuse large B-cell lymphoma.
Authors: Johannes Duell, Pau Abrisqueta, Martin H. Dreyling, Gianluca Gaidano, Eva González Barca, Wojciech Jurczak, Kami J. Maddocks, Tobias Menne, Olivier Tournilhac, Abhishek Bakuli, Aasim Amin, Konstantin Gurbanov, Gilles A. Salles, Zsolt Nagy
Journal: Journal of Clinical Oncology (2023)

e19522 Background: The Phase II L-MIND study led to accelerated US approval and EU conditional authorization of the CD19-targeted immunotherapy, tafasitamab, + lenalidomide (LEN) followed by tafasitamab monotherapy for patients (pts) with R/R DLBCL ineligible for autologous stem cell transplant (ASCT). Long-term L-MIND data further support the regimen. Here we present exploratory analyses of final 5-year (yr) efficacy in subgroups of interest. Methods: Pts (≥18 years) with ASCT-ineligible R/R DLBCL, 1–3 prior systemic therapies (incl. ≥1 targeting CD20) and ECOG PS 0–2 received tafasitamab for ≤12 28-day cycles (+ LEN), then alone until disease progression. Primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Exploratory subgroup analyses including by International Prognostic Index (IPI) and time to progression after 1L (in pts with only 1 prior line) used Kaplan-Meier estimates of 5-yr endpoints. Results: As of 14 Nov, 2022 in the full analysis set (FAS; n=80), ORR was 56.2% [95% CI: 44.7–67.3]. Median treatment duration was 9.0 months (mo) [0.5–73.6] and median follow-up (mFU) for OS was 65.6 mo [59.9–70.3]). Median DoR was not reached (mFU: 43.7 mo [29.9–58.4]). Of 18 patients in follow-up for ≥5 years, 9 received tafasitamab until end of study per protocol, 9 discontinued while in remission. RR and 5-yr rates for DoR, PFS and OS showed long-term clinical activity in all pt subgroups (Table). Conclusions: In this 5-yr subgroup analysis, a long-term clinical benefit with tafasitamab + LEN followed by tafasitamab monotherapy was observed in all subgroups of clinical interest, including pts with poor prognosis risk factors. These data suggest this immunotherapy may have curative potential, which is being explored in further studies. Clinical trial information: NCT02399085 . [Table: see text]
Oregovomab and non-platinum chemotherapy in PARP inhibitor-resistant ovarian, fallopian tube, or primary peritoneal cancer patients not candidates for platinum retreatment: A multicenter, two-cohort, single-arm phase 2 trial (OPERA/KGOG 3065/APGOT-OV6).
Authors: JUNG-YUN LEE, Junsik Park, Chel Hun Choi, Hyun Woong Cho, Jae Hong No, Dae Gy Hong
Journal: Journal of Clinical Oncology (2023)

TPS5621 Background: As PAPR inhibitors (PARPis) are becoming the standard of care option for epithelial ovarian cancer (EOC), PARPi-resistant patients are increasing. Moreover, non-platinum single agent chemotherapy in these patients has been found to elicit poor survival outcomes. Oregovomab, an investigational murine monoclonal antibody directed against CA-125, has shown promising efficacy in the previous phase II study of combinational front-line adjuvant chemotherapy. The aim of the present study is to investigate the efficacy of oregovomab + non-platinum-based chemotherapy in PARPi-resistant EOC patients not suitable for platinum-based therapy. Methods: OEPRA is a multi-centre, investigator-initiated, two-cohort, single-arm phase II trial recruiting PARPi-resistant EOC patients from five sites in South Korea. The trial includes patients with recurrent EOC who have experienced disease progression despite treatment with PARPis and who have either received bevacizumab or are not eligible for bevacizumab treatment. Mucinous histology type is excluded. Patients who have received one to three prior lines of chemotherapy are to be assigned to Cohort 1 (oregovamab 2 mg [C1,2,3,5,7 for five doses] + pegylated liposomal doxorubicin [PLD] 40 mg/m 2 q4w, n = 28), while patients who have received more than three prior lines of chemotherapy are to be assigned to Cohort 2 (oregovamab 2 mg [C1,2,3,5,7 for five doses] + weekly paclitaxel 80 mg/m 2 [D1,8,15 q4w], n = 28). A total of 56 patients will be recruited and treated with oregovomab + PLD / weekly paclitaxel until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint is objective response rate by RECIST 1.1. Accrual is expected to be completed in 2023, followed by presentation of results in 2024. The study is registered with Clinicaltrials.gov (NCT05407584). Clinical trial information: NCT05407584 .
A phase 2 study of the combination of decitabine (DAC), venetoclax (VEN), and ponatinib in patients (Pts) with chronic myeloid leukemia (CML) in accelerated phase (AP)/myeloid blast phase (MBP) or Philadelphia-chromosome positive (Ph+) acute myeloid leukemia (AML).
Authors: Jayastu Senapati, Farhad Ravandi, Courtney Denton Dinardo, Ghayas C. Issa, Koji Sasaki, Marina Konopleva, Walid Macaron, Lewis Fady Nasr, Marianne Zoghbi, Cedric Christophe Nasnas, Naveen Pemmaraju, Kelly Sharon Chien, Maro Ohanian, Elias Jabbour, Abhishek Maiti, Hagop M. Kantarjian, Nicholas James Short
Journal: Journal of Clinical Oncology (2023)

e19044 Background: CML-AP/MBP and Ph + AML are therapeutic challenges. Based on published pre-clinical data of synergism (Leonard et.al., Sci Transl Med 2016), we hypothesized that combining ponatinib with DAC and VEN might lead to high rates of response and facilitate allogeneic stem cell transplantation (SCT). Methods: The study (NCT04188405) enrolled pts ≥ 18 years of age with CML-AP, CML-MBP or Ph + AML with ECOG PS ≤ 3 and adequate liver/renal function. Pts with significant uncontrolled cardiovascular comorbidities were excluded. Therapy was with DAC (20 mg/m 2 /day) x 5 days, VEN (400 mg equivalent dose/day) x 21 days, and ponatinib (45mg/day) x 21 days in cycle 1 and then continuously in cycles 2-24. Each cycle was for 28 days. Ponatinib was reduced to 30mg/day for pts in CR/CRi and to 15 mg/day for pts in CMR. Intrathecal prophylaxis with 4 doses of cytarabine was recommended. The primary objective was to determine the overall response rate (ORR) with the regimen. Results: From Jul 2020 to Jan 2023, 15 pts were treated, 4 with CML-AP, 10 with CML-MBP and 1 with Ph + AML (Table). 11 pts (73%) had prior TKI exposure, including 4 pts with prior ponatinib. 5 of 13 tested pts (38%) had an ABL1 kinase domain mutation (T315I, Q252H, L384M in 1 pt each and E255K in 2 pts). The median number of cycles received was 3 (range, 1-7). 11 pts (73%) responded; 6 pts (40%) with CR/CRi and 5 (33%) with MLFS. Best response was achieved after cycle 1 in 9 of 11 (82%) responders. All 4 pts with CML-AP responded, and 9 of 11 pts (82%) with prior TKI exposure responded. Four pts underwent subsequent SCT. At a median follow-up of 9.8 months, the median overall survival (OS) was 11.0 months, and the estimated 10-month OS was 63%. The median relapse-free survival was 5.7 months. Among the 11 responders, 5 relapsed (one after SCT), and 6 are in ongoing response (3 after SCT). One pt had a related grade 3 mucositis. No grade 4-5 related non-hematological adverse events were observed. Of the 10 pts who received &gt; 1 cycle of therapy, 5 pts had delay (&gt;1 week) in initiation of subsequent cycles due to cytopenias. The 60-day mortality rate was 0%. Two pts died on study, one from leukemia and one from infection while in MLFS. Conclusions: A triplet combination of DAC, VEN and ponatinib was well-tolerated and resulted in an ORR of 73% in this poor-risk population of pts with advanced Ph + leukemias. Clinical trial information: NCT04188405 . [Table: see text]
Genetic counseling and testing for epithelial ovarian cancer in a diverse patient population.
Authors: Kee-Hwan Michael Kim, Judy Hayek, Cheyenne Acker, Anjile An, Peilin Zhang, Constantine Gorelick, Margaux Jenna Kanis
Journal: Journal of Clinical Oncology (2023)

e17563 Background: According to the current American Society of Clinical Oncology (ASCO) guidelines, “all women diagnosed with epithelial ovarian cancer should be offered germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes, irrespective of their clinical features or family history”. Test results have implications for surveillance, familial testing, and treatment. We investigated how genetic counseling and testing rates at a New York City tertiary care center with a large minority population compared with national rates, and if any disparities existed. Methods: This is a retrospective cohort study of patients with newly diagnosed epithelial ovarian, fallopian tube, peritoneal cancer between January 2014 and June 2022. Data were obtained from pathology and chemotherapy databases at the NewYork-Presbyterian Brooklyn Methodist Hospital. Variables including age, race, ethnicity, BMI, insurance, language, family history of cancer, date of diagnosis, stage, and genetic counseling/testing status were manually extracted. Descriptive statistics were used to characterize the variables of interest. Chi-square/Fisher’s exact tests were used to examine the association between genetic counseling/testing and categorical variables. Wilcoxon rank-sum/t-tests were used for association between continuous factors. The Mann-Kendall trend test was used to assess year-to-year trends. Results: 144 patients were identified. Mean age at diagnosis was 63 years (SD:13). This diverse cohort included 51% white, 36% black, 3.5% Asian, 9% other/unknown; 9% were of Hispanic ethnicity and 26% were non-English speaking. 104 (72%) patients received genetic counseling and 99 (69%) received subsequent genetic testing. 95% of those that underwent genetic counseling underwent subsequent testing. The genetic counseling and testing rates were not influenced by race, ethnicity, language, insurance type, BMI, family history of cancer. It was associated with significant difference by cancer stage (p &lt; 0.01). There was a significant upward trend of proportion of patients that received genetic counseling from 47% in 2015 to 100% in 2022 (p &lt; 0.01). Most genetic counseling was performed by a gynecologic oncologist (93%) as opposed to a genetic counselor (6.7%). Overall, 12 (8.3%) patients were BRCA+. Conclusions: Genetic counseling and testing rates within this diverse study population proved to be at least twice as high as the national average of 10-30%, with an increasing year-to-year trend. There were no disparities observed, in contrast to previously published data. BRCA mutation detection was in line with established prevalence within ovarian cancer, indicating adequate screening. Concentrated efforts on behalf of oncologists ensures excellent access to testing.
Single-cell analysis of CD8<sup>+</sup> T-cells by sex in renal cell carcinoma.
Authors: Ning Kang
Journal: Journal of Clinical Oncology (2023)

e16501 Background: Although sex bias has been reported in the development and progression of renal cell carcinoma (RCC), the underlying mechanisms remain enigmatic. Here, we investigated the sex differences in the tumor microenvironment (TME) of RCC patients and explored a promising combination drug regimen to enhance the efficacy of immunotherapy. Methods: Single-cell RNA sequencing (scRNA-seq) data from four published datasets were analyzed to investigate the sex differences in RCC patients, and tumor tissues were collected to validate the sex differences using multiplex immunofluorescence (MxIF) and flow cytometry (FCM). The function of the androgen-androgen receptor axis in sex differences was explored in vivo and in vitro experiments. Results: By analyzing the scRNA-seq data of 220,156 cells and MxIF and FCM assays, we found that CD8 + T-cells infiltrated highly in the TME of male RCC, but mainly presented an exhausted and dysfunctional state. In vitro and in vivo experiments indicated that the dysfunction and exhaustion of CD8 + T-cells in male TME were induced by androgen. Clinically, higher serum androgen was significantly associated with a worse prognosis in male RCC patients receiving immunotherapy. Androgen receptor inhibitors could activate tumor-infiltrating CD8 + T-cells and enhance the efficacy of immunotherapy of RCC in vivo. Conclusions: We delineated the difference in TME between male and female patients with RCC, and demonstrated that the androgen-androgen receptor axis plays an important role in immunosuppression in male RCC. Clinically, androgen receptor inhibitors plus immunotherapy can be a promising combination regimen in RCC patients.
Efficacy and safety of camrelizumab and apatinib combined with neoadjuvant concurrent chemoradiation for MSS locally advanced rectal cancer.
Authors: Tao Jiang, Dongsheng Wang, Jingjing Cheng, Xiaojuan Wei, Jialei Fu, Lianjing Cao, Peijie Lei, Xianxiang Zhang, Yuan Gao, Jilin Hu, Hongjun Zhang, Bin Cao, Baoguo He, Qingdong Mao, Peng Qi, Jigang Wang, Xiaoming Zhou, Junying Tan, Haijun Lu
Journal: Journal of Clinical Oncology (2023)

e15647 Background: Long-term neoadjuvant concurrent chemoradiotherapy (CRT) is the standard therapy for local advanced rectal cancer (LARC).However, the pCR rate is only about 15 %. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in advanced rectal cancer, but their efficacy in the neoadjuvant setting is unclear. In this exploratory trial, we evaluate the efficacy and safety of a combination of ICI (Camrelizumab), anti-angiogenesis (Apatinib) and CRT for neoadjuvant treatment of microsatellite-stable (MSS) LARC. Methods: Patients in experimental group received Camrelizumab injection combined with Apatinib tablets and concurrent CRT. Radiotherapy dose: 5040cGy/28f/180cGy; Capecitabine 825 mg/m2 bid on the radiotherapy day; Apatinib 250mg qd d1-d60; Camrelizumab 200 mg q3w, d22, d43, d64. Surgery with total mesorectal excision was performed 7-9 weeks after the end of CRT. The primary endpoint was pCR rate and the secondary endpoints included major pathological response (MPR) rate, R0 resection rate, 2-year DFS rate, 3-year OS rate and safety. Results: From July/2022 to October/2022, a total of 11 patients were recruited and assessed, 90.91% (10/11) of which is at high-risk (cT3 with any MRF involved, any cT4a/b, lateral node +, HLARC). Out of the 11 patients evaluable for pathological response, 4 (36.36%) patients achieved a pCR (AJCC grade 0) and 7 (63.64%) obtained a MPR(AJCC grade 0+1)(table). All patients achieved R0 resection and downstaging. Treatment-related severe adverse events were observed in 3 patients (grade 3-4 transaminase elevations); all fully recovered and received radical surgery. No treatment-related deaths were observed. Conclusions: A promising pCR rate of 36.36%, with mild toxicities, was shown in MSS LARC patients treated with neoadjuvant Camrelizumab combined with Apatinib and long-term CRT plus radical surgery, suggesting the candidate therapy for the future non-surgical approach. Clinical trial information: ChiCTR2100053040 . [Table: see text]